The problems associated with oral administration of therapeutic agents such as polypeptides are well known in the pharmaceutical industry and various strategies are being used in attempts to solve them. Delivering therapeutic polypeptides through the gastrointestinal tract is difficult due to the presence of high amounts of polypeptide degrading enzymes in the stomach and the intestine. To achieve oral delivery, the therapeutic polypeptide must both survive the gastrointestinal enzymes and must have an ability to be transported through or around the enterocytes of the intestine.
Examples of approaches to oral delivery include 1) the use of enzyme inhibitors to slow the rate of degradation of polypeptides and polypeptides in the gastrointestinal tract; 2) manipulation of pH to inactivate local digestive enzymes; 3) the use of permeation enhancers to improve the absorption of polypeptides by increasing their paracellular and transcellular transports; 4) the use of nanoparticles as particulate carriers to facilitate intact absorption by the intestinal epithelium, especially, Peyer's patches, and to increase resistance to enzyme degradation; and 5) the use of liquid emulsions to protect the drug from enzymatic degradation in the intestinal lumen.
Oral dosage forms used for delivery of conventional small molecule drugs have also been used in attempts to improve oral delivery of polypeptides. Except for cases where the polypeptide has been chemically modified or where a proprietary absorption enhancer has been used, the results have been disappointing. To the inventors' knowledge, there have been only a handful of human clinical trials demonstrating adequate bioavailability and pharmacokinetics to suggest that commercializing an orally delivered polypeptide is feasible.
There is a need in the art for new approaches to formulating polypeptide drugs for oral delivery that improves upon the current state of the art by enabling larger amounts of drugs to enter the bloodstream through the gastrointestinal tract.